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Old 02-09-2011, 11:44 PM   #1
Lani
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new targets being discovered for inflammatory bc

J Cell Physiol. 2011 Feb 1. doi: 10.1002/jcp.22620. [Epub ahead of print]
Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer.
Baillo A, Giroux C, Ethier SP.

Wayne State University Department of Oncology, Karmanos cancer Institute, Wayne State University, Detroit, Mi; Wayne State University Department of Oncology, Karmanos cancer Institute, Karmanos cancer Institute, Detroit, Mi.
Abstract
We have previously shown that SUM-149 human breast cancer cells require an AREG/EGFR autocrine loop for cell proliferation. We also demonstrated that AREG can increase EGFR stability and promote EGFR localization to the plasma membrane. In the present studies we successfully knocked-down AREG expression in SUM-149 cells by lenti-viral infection of AREG shRNA. In the absence of AREG expression, SUM-149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by western blot. Immunofluorescence and confocal microscopy showed that following AREG knock-down, EGFR continued to localize to the cell surface. Soft agar assays demonstrated that AREG knock-down cells retain anchorage-independent growth capacity. Additionally mammosphere forming assays and Adefluor staining analysis showed that knock-down of AREG expression did not affect the expression of stem cell phenotypes. However, following AREG knock-down, SUM-149 cells demonstrated a dramatic decrease in their ability to invade a Matrigel matrix. Consistent with this observation, microarray analysis comparing cells infected with a non-silencing vector to the AREG knock-down cells, identified genes associated with the invasive phenotype such as RHOB and DKK1, and networks associated with cell motility such as integrin-linked kinase signaling, and focal adhesion kinase signaling. AREG was also found to modulate WNT and Notch signaling in these cells. Thus, AREG functions in regulating the invasive phenotype, and we propose that this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR. 2011 Wiley-Liss, Inc.

Copyright 2011 Wiley-Liss, Inc.
PMID: 21302279 [
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Old 02-12-2011, 05:02 AM   #2
Ellie F
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Re: new targets being discovered for inflammatory bc

Thanks Lani
Could you try to explain ANY of it to me. I would really appreciate it.

Thanks Ellie
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Old 02-12-2011, 06:22 AM   #3
Midwest Alice
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Re: new targets being discovered for inflammatory bc

Hi Lani and Ellie, I too am interested in knowing what the study means. Looks like progress and this is good!!

~Alice
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Alice
04/08 age 50 III IBC Her2+++ ER/PR-8cm 14/14 Double M, Body and Brain CT/PET clear, ? on spine,Muga 53
06/08, 4 A/C, Neulasta
08/08, Herceptin/tax 12 every week
10/08, CT/PET clear, ? on pelvis, hips, MUGA 43, started Enalaprial for heart, Herceptin every 3 weeks
11/08 33Rads; 12/08 MUGA 48
2/09 MRI spine and bone scan, old mets to spine, Chest x-ray, blood work, IV NED,regular CPAP use,Zometa x6, first -flue like symptoms 2 days;Herceptin x3; stage 2 lymphoedema..sleeve and glove
4/09 Brain MRI - CLEAR; MUGA 54
7/09 chest ultrasound,
10/09 PET, brain and spin MRI NED Herceptin only. MUGA 59!!!
1/11 Hip replacement 7/11 Hip 2 replacement
4/12 4 years!! Herceptin
6/12 start reconstruction finish in 12/12
2/14 Herception - 6 years!!!

1 Corinthians 10:13 "No temptation has seized you except what is common to man. And God is faithful; he will not let you be tempted beyond what you can bear. But when you are tempted, he will also provide a way out so that you
can stand up under it."

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Old 02-13-2011, 06:24 PM   #4
Lani
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Re: new targets being discovered for inflammatory bc

this article discusses techniques used to prove the necessity for certain genes/proteins/receptors to maintain growth and invasion of IBC

It also discusses which work in concert, which work as competitors

among the targets (the more specific the target, the less side-effects) are:

EGFR (FDA has already approved drugs)
Amphiregulin (a ligand rather than a receptor), aka AREG
DKK1
RHOB
networks associated with cell motility such as integrin-linked kinase signaling, and focal adhesion kinase signaling.
Wnt signalling
Notch signalling-- there are already trials of a gamma-secretase inhibitor in bc

Hope this helps!
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